Herpes simplex virus (herpes simplex virus type 1, or HSV-1, and herpes simplex virus type 2, or HSV-2) produce a variety of infections involving vesicular eruptions on the skin and mucus membranes, and may also affect the central nervous system and occasionally visceral organs. HSV-1 is associated mainly with the oral region (oral herpes) and causes cold sores and fever blisters. HSV-2 causes lesions that are similar to oral herpes, but that occur mainly in the genital region (genital herpes). Herpes viruses are particularly deleterious pathogens because of their potential for persistence in cells, their transformation of normal cells into cells showing uncontrollable proliferation, and their affinity for nerve tissue. Once herpes viruses have infected, they may persist in the host cells. For example, after infecting epithelial cells, herpes simplex viruses secondarily invade nerve tissues and remain latent in them. With HSV-1, latency occurs in facial nerve tissue (the trigeminal ganglion). HSV-2 establishes latency in the sacral ganglia, which are in the pelvic region. P. J. VanDemark and B. L. Batzing, The Microbes (1987).
Most people have been infected with HSV-1 by the time they reach adulthood; about half of children between one and five years old have been infected. As a consequence of latency, herpes viruses may appear periodically to cause recurrent disease. Recurrence is common, and may be stimulated by various physiological stresses, trauma, emotional stress, and hormonal changes.
HSV-2 is a particuarly important public health problem. First, it is a sexually transmitted disease for which there is no cure. In 1987, the annual incidence of HSV-2 infection in the United States alone was estimated to be in the range of 200,000-500,000 cases. Depending on the level of sexual activity and socioeconomic factors, the overall prevalence of HSV-2 virus in the population has been estimated to be within 10% and 70%. Additionally, if HSV-2 infection is transmitted to newborns during birth, the subsequent infection may be devastating. It has been estimated that at least 50% of newborns delivered by women with genital herpes become infected with HSV-2; about half of these infants suffer severe virus-induced defects, such as retardation. Thirdly, there are numerous associations between herpes virus infections and the contracting or development of other serious diseases. For example, there is an established link between HSV-2 infection and cervical cancer. Herpes virus has been shown to transform normal cells into cancer cells under laboratory conditions. HSV-2 infection has also been found to be a risk factor for the acquisition and transmission of infection of HIV-1, the virus thought to be the cause of AIDS. HSV-1 is also associated with the incident of other diseases, such as viral encephalitis.
Several methods have been proposed and used as treatments for herpes infection, including the administration of various pharmaceuticals, such as iododeoxyuridine, adenine arabinoside (ara-A) and acycloguanosine (acyclovir). Iododeoxyuridine and ara-A are used to treat HSV-1 eye infections, while ara-A may reduce the severity of encephalitis caused by HSV-1 and HSV-2 infection of newborns. Acyclovir is currently considered to be the mainstay of drug therapy in the treatment of herpes, both genital and oral. However, none of these methods has proved to be entirely effective. For example, while acyclovir has been shown to speed the healing and resolution of genital herpes infections, the benefit of treating acute episodes of recurrent genital disease is quite modest and not recommended as a long-term therapy. L. Corey, "Herpes Simplex Viruses" in Harrisons' Principles of Internal Medicine 13th Edition, K. J. Isselbacher et al., eds., p. 786 (1994). Acyclovir has a very limited benefit with regards to oral herpes; in many cases, developing lesions are not aborted and healing time is not reduced. Most seriously, acyclovir-resistant strains of herpes viruses are being idenitified with increasing frequency, especially in HIV-infected person. There is therefore a desire to develop a method of treating herpes infections that is effective, safe and practical.